In this proposed study of scleroderma (PSS), we propose to focus our efforts on the contrasts between inactive and the early and active phases of the disease, including those present in the undifferentiated (mixed) connective tissue disease syndrome. We hope that by defining certain immunopathologic events in relation to these studies of activity we may learn more about the etiology and the basic immune processes which precede or accompany full developed PSS. The aim of the study are several: a) Clinical disease activity will be monitored over time and correlated with immunologic abnormalities (autoantibodies, circulating immune complexes, circulating T-lymphocytes and monocytes, serum interferon), and changes within the dermis (immune deposits, collagen types, mononuclear cell infiltration) to demonstrate a marker(s) of disease activity. b) To define an antigen, which may lead to lymphocyte activation in the cell mediated immune response, which appears to be responsible for the ultimate tissue insult. Antigen definition will be achieved by isolating immune complexes from serum and raising an heterologous antibody to the contained antigen. c) To characterize the material in serum which is toxic to endothelial cells. We plan to study its cellular specificity; determine if it represents a proteolytic enzyme or lymphokine and its effect on collagen synthesis.